Aldose reductase, a member of the multi-gene aldo-keto reductase family, has been implicated in the etiology of diabetic complications which can affect many tissues, but especially eye, nerve and kidney. Most previous studies of aldose reductase, including development of aldose reductase inhibitors as potential therapeutic drugs, have utilized animal sources of aldose reductase, whose properties differ markedly from human aldose reductase. Recently, methods were developed that allow isolation of human aldose reductase without alteration of its native properties. The objective of the study is to analyze the kinetic and drug binding properties of human aldose reductase in order to establish a firm enzymological foundation upon which to develop future therapeutic drugs. The Specific Aims are as follows: 1. To determine whether the multiple form of human aldose reductase represent different gene products. 2. To analyze the kinetic properties of the multiple forms of human aldose reductase with emphasis on glucose as substrate. 3. To analyze the drug binding properties of human aldose reductase.